Abstract
SEPT9 is a mammalian septin family member. There is growing evidence that SEPT9 plays a role in cancer. The protein product, SEPT9_V1, associates with microtubules and interacts with hypoxia-inducible factor (HIF)-1alpha, the regulated subunit of the key transcription factor HIF-1. HIF-1 transcriptional activity is thoroughly dependent on intact microtubules. We tested the hypothesis that SEPT9_V1 confers resistance to microtubule-mediated HIF-1 inhibitors. SEPT9_V1 protein expression was strongly correlated with susceptibility of a wide range of cancer cells to 2-methoxyestradiol and paclitaxel. Our results revealed that SEPT9_V1 could serve as a biomarker for therapeutic resistance to microtubule disrupting agents.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
2-Methoxyestradiol
-
Antineoplastic Agents / pharmacology*
-
Benzoquinones / pharmacology
-
Cell Line, Tumor / drug effects
-
Cell Line, Tumor / metabolism
-
Drug Resistance, Neoplasm / physiology*
-
Estradiol / analogs & derivatives*
-
Estradiol / pharmacology
-
GTP Phosphohydrolases / biosynthesis
-
GTP Phosphohydrolases / genetics
-
GTP Phosphohydrolases / physiology*
-
Gene Expression Regulation, Neoplastic / drug effects
-
Gene Expression Regulation, Neoplastic / physiology
-
Humans
-
Hypoxia-Inducible Factor 1, alpha Subunit / physiology
-
Indazoles / pharmacology
-
Lactams, Macrocyclic / pharmacology
-
Neoplasm Proteins / biosynthesis
-
Neoplasm Proteins / genetics
-
Neoplasm Proteins / physiology*
-
Paclitaxel / pharmacology*
-
Protein Isoforms
-
RNA Interference
-
RNA, Messenger / biosynthesis
-
RNA, Messenger / genetics
-
RNA, Neoplasm / biosynthesis
-
RNA, Neoplasm / genetics
-
Recombinant Fusion Proteins / physiology
-
Septins
-
Transcription, Genetic / drug effects
-
Transcription, Genetic / physiology
-
Tubulin Modulators / pharmacology*
Substances
-
Antineoplastic Agents
-
Benzoquinones
-
HIF1A protein, human
-
Hypoxia-Inducible Factor 1, alpha Subunit
-
Indazoles
-
Lactams, Macrocyclic
-
Neoplasm Proteins
-
Protein Isoforms
-
RNA, Messenger
-
RNA, Neoplasm
-
Recombinant Fusion Proteins
-
Tubulin Modulators
-
3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole
-
tanespimycin
-
Estradiol
-
2-Methoxyestradiol
-
GTP Phosphohydrolases
-
SEPTIN9 protein, human
-
Septins
-
Paclitaxel